Síntese e reatividade de N-alquinilindóis: preparação de N-alquinilindóis-2-substituídos e calcogenazolo[3,2-a]indóis

• Ano de defesa: 2020
• Autor(a) principal: Prochnow, Thaís
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; Química; UFSM; Programa de Pós-Graduação em Química; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Calcogênio; Ciclização; Indol; Chalcogen; Cyclization; Indole; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/22932

This work reports the preparation of 2-Substituted-N-alkynylindoles 3 (18 examples) with yields that varied from 30 to 90%, via the metalation reaction of N-alkynylindoles 1 followed by the capture of 2-indolyl lithium intermediate with different electrophiles 2. In order to evaluate the versatility of the 2-Substituted-N-alkynylindoles compound 3j, it was subjected to reaction with CBr4/PPh3 for the synthesis of 2-gem-dibromovinyl N-alkynylindoles 3ja, which was obtained in 75% yield, and 2-Substituted-N-alkynylindoles 3a through hydrotelluration it was possible to obtain vinylic tellurides 3aa in 55% yield. In addition, compounds 3e, 3f and 3l showed AChE inhibitory potential the low micromolar range similar to that obtained with donepezil, a commercially available cholinesterase inhibitor. In a second step, a methodology was also developed in the absence of transition metal, with N-alkynylindoles 1 and n-butyllithium, from the addition of elemental chalcogen (S, Se and Te) and an alkyl halide, the cascade reaction proceeded selectively through an intramolecular 5-endo-dig cyclization forming two new carbon-chalcogen bonds, where it was possible to synthesize 21 new compounds - chalcogenazolo[3,2-a]indoles 4, with yield in the range of 35 to 71%. In order to expand the methodology, the chalcogenolate anion intermediate was subjected to an oxidation reaction in the presence of air, which led to 3 diselanes selenazolo[3,2-a]indoles 5 derivatives in good yields between 44 and 65%, and also ditellane tellurazolo[3,2-a]indoles 5 (3 examples) with a yield of 36 to 47%.